The field of the invention is the diagnosis of hepatocellular carcinoma (HCC).
Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer worldwide. Incidence of the disease varies geographically from between 1 in 5,000 in Asia to 1 in 20,000 in western nations (Wildi et al., 2002). Patients with chronic liver disease are at increased risk for development of hepatocellular carcinoma. This is particularly true for individuals with liver cirrhosis who should be closely monitored for development of this disease.
Currently, it is difficult to diagnose HCC. Methods employed generally rely on imaging techniques such as MRI, CT, and ultrasound and are of little use in detecting the disease in its earliest stages. As with most cancers, early detection of HCC would leave physicians with more treatment options and patients with a better prognosis (Befeler and Bisceglie, 2002).
Better imaging reagents would enhance the sensitivity and broaden the applicability of currently used scanning methodologies. Proteins expressed specifically or preferentially on the surface of HCC cells could be targeted by an antibody or other targeting reagent that is conjugated to an imaging agent. Such conjugates would aid in diagnosis of the disease at an early stage.
The literature describes a few serodiagnostic markers indicative of HCC, including alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction (AFP-L3), and des-gamma-carboxy prothrombin or PIVKA-II (Shimizu et al., 2002; Ikoma et al., 2002; Fujiyama et al., 1986; Naraki et al., 2002). Unfortunately, at best, elevated levels of these serum proteins are detected in only about 50% of HCC patients. A significant increase in the sensitivity of HCC diagnosis can be achieved by combining tests for AFP, AFP-L3 and PIVKA-II. However, even when all three tests are combined, the sensitivity is only about 87% (Fujiyama et al., 2002).
Identification of new serodiagnostic markers specific to HCC and present in a large percentage of HCC patients would greatly improve the diagnosis of this disease and be more cost effective than commonly used scanning methodologies and/or the combined use of all currently available serodiagnostic assays.
These and other limitations and problems of the past are solved by the present invention.